Diabetes is a complex disease caused by the body's failure to produce adequate insulin or a cell's failure to respond to insulin, resulting in high levels of glucose in the blood. Type I diabetes is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas in genetically predisposed individuals. There is no current cure, and treatment by injection or infusion of insulin must be continued indefinitely. Type II diabetes is a metabolic disorder brought on at any age by a combination of lifestyle, diet, obesity, and genetic factors. The World Health Organization recently revised its findings from a study conducted in 2004 with predictions that by 2030, 10% of the world's population of all ages will have either Type I or Type II diabetes. This translates to roughly 552 million people worldwide suffering from some form of this disease.
Typically, treatment for diabetes requires both repeated checking of blood glucose levels and several injections of insulin as prescribed by the physician throughout the day, since insulin cannot be taken orally. Major drawbacks of such treatment are the constant need to draw blood and test glucose levels throughout the day, improper or low dosage amounts of insulin, contamination of the insulin delivery system, lifestyle restriction, the unfortunate potential development of subcutaneous scar tissue due to repeated injections at the same location, and the high cost of medication, testing strips, and other treatment related materials.
Diabetes is usually controlled by insulin replacement therapy in which insulin is delivered to the diabetic person by injection to counteract elevated blood glucose levels. Recent therapies include the basal/bolus method of treatment in which a basal dose of a long-acting insulin medication, for example, Humalog® and Apidra®, is delivered via injection once every day, or, in the alternative, gradually throughout the day. The basal dose provides the body with an insulin profile that is relatively constant throughout the day, or could follow a profile best-suited for the particular diabetic patient. These rates can change based on the patient's response to insulin. At mealtime, an additional dose of insulin, or bolus, may be administered based on the amount of carbohydrate and protein in the meal. The bolus dose is viewed as an emergency response to spikes in blood sugar that need to be brought down by injection of insulin. Accurate calculations of various parameters, including, but not limited to, the amount of carbohydrates and proteins consumed, and the lapse in time since the last dosage are necessary to determine the appropriate dosage of insulin. The dosages are thus prone to human error and the method is ineffective when doses are skipped, forgotten, or miscalculated. Exercise, stress, and other factors can also cause the calculations to be inaccurate. Bolus doses are usually administered when the patient's glucose level is high or above certain acceptable thresholds and needs immediate attention.
To address these and other problems, insulin delivery devices or pumps were developed to mimic the way a normal, healthy pancreas delivers insulin to the body. Innovations are rapidly advancing toward the creation of a closed-loop insulin delivery system or “artificial pancreas.” These systems employ real-time glucose-responsive insulin administration via continuous glucose monitoring and wireless communication with a controller which dispenses insulin based on tightly controlled algorithms. The two main algorithmic systems used to calculate insulin dosages automatically are the proportional-integral-derivative (“PID”) control and the mathematic-predictive control (“MPC”). MPC algorithms can be considered proactive or predictive. They forecast glucose levels in anticipation of meals, physical activity and administer insulin over a prediction window of 1.5 to 3 hours or longer. PID algorithms, however, are considered reactive in response to measured glucose levels and cannot predict dosages. Unfortunately, there is currently no industry-wide standard in place for embedded algorithmic calculations, and dose calculations vary from device to device.
Often, both methods are utilized when insulin is coadministered with glucagon or other medication, although in computer simulations, glycemic regulation via MPC calculations may achieve superior glucose regulation. The future of this treatment protocol may depend on several factors: more accurate glucose sensors, rapid response software and hardware, single catheters for both glucose sensing and medication diffusion, and dual or multi-chambered medication delivery cartridge systems.
Recent innovations suggest that the addition of amylin analog hormone therapy, administered along with insulin and glucagon, delays glucose absorption and improves post-meal glucose control. Type 1 diabetics often lack counterregulatory hormones like amylin, which is usually secreted with insulin in the healthy pancreas. The goal with diabetes treatment protocol is to achieve normoglycemia, or an HbA 1c less than approximately 6.5%, a fasting glucose below approximately 100 mg/dL, postprandial glucose below approximately 140 mg/dL, and the avoidance of hypoglycemic excursions. Thus, the ability to deliver multiple medications simultaneously or independently would be highly desirable.
One recurring problem with most conventional miniaturized ambulatory infusion pumps is that the amount of medication which can be stored in the reservoirs often cannot meet the needs of certain diabetic patients. Many Type II diabetics who require insulin often need more insulin per gram of carbohydrate due to a condition referred to as “insulin resistance.” Additionally, many diabetic therapies include one or more medications delivered alternately or simultaneously. For this reason, a medication pump which employs a plurality of reservoirs able to dispense medication at variable rates is highly desirable. Therefore, a substantial need exists to best maximize the volume of the medication reservoirs while maintaining a very small overall size of the device itself.
With the demand for a decrease in size of the pump unit also comes a decreased size in the medication reservoir. This reduced reservoir size means more frequent refilling, greater potential for contamination of the reservoir, more frequent changes of the cannula and tubing, and greater expense overall in treating the condition. Frequent manual refilling of a medication reservoir can also lead to the increased formation of bubbles, which is a significant problem. Even very small bubbles of 10 microliters or less can displace enough fluid to equal a missed dose of 1 unit of medicament. Insulin medication itself can also form bubbles when dissolved air is “outgassed” through normal changes in temperature or atmospheric pressure. Therefore the need exists to provide a disposable, prepressurized, prefilled medication reservoir that can work as part of a medication pump system to provide extremely accurate delivery of a plurality of medications.